Preparation of two sets of 5,6,7-trioxygenated dihydroflavonol derivatives as free radical scavengers and neuronal cell protectors to oxidative damage

被引：29

作者：

Gong, Jingxu ^{[1
,3
]}

Huang, Kexin ^{[1
]}

Wang, Feng ^{[2
]}

Yang, Leixiang ^{[2
]}

Feng, Yubing ^{[2
]}

Li, Haibo ^{[2
]}

Li, Xiaokun ^{[1
]}

Zeng, Su ^{[2
]}

Wu, Xiumei ^{[1
]}

Stoeckigt, Joachim ^{[2
,4
]}

Zhao, Yu ^{[1
,2
]}

Qu, Jia ^{[1
]}

机构：

[1] Wenzhou Med Coll, Key Lab So Zhejiang TCM R&D, Sch Pharm, Wenzhou 325035, Peoples R China

[2] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China

[4] Johannes Gutenberg Univ Mainz, Lehrstuhl Pharmazeut Biol, Inst Pharm, D-55099 Mainz, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 09期

关键词：

5,6,7-Trioxygenated dihydroflavonols; cis-Dihydroflavonoids; Antioxidant; Lipid peroxidation; Free radical scavenger; PC12; cells; Xanthine oxidase inhibitor; XANTHINE-OXIDASE; STRESS; FLAVONOIDS; BAICALEIN; INHIBITION;

D O I：

10.1016/j.bmc.2009.03.032

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

An unusual class of 5,6,7-trioxygenated dihydroflavonols (3a-e and 4a-j) were designed and prepared. Their antioxidative properties were assessed by examining their capacities in several in vitro models, including superoxide anion and 1,1-diphenyl-2-picrylhydrazyl ( DPPH) radical scavenging, rat liver homogenate lipid peroxidation inhibition, PC12 cells protection from oxidative damage, and xanthine oxidase inhibition. These dihydroflavonols displayed positive quenching abilities towards O-2(center dot-) and DPPH free radicals, in which the majority exhibited superior antioxidant properties to Vitamin C. cis-Configurated compound (+/-)-3e demonstrated remarkable inhibition to LPO with an IC50 value of 1.9 +/- 0.3 mu M, which was apparently stronger than that of quercetin (IC50 = 6.0 +/- 0.4 mu M). trans-Configurated dihydroflavonol (+/-)-4h exhibited significant protective effect on PC12 cells against oxidative damage with an EC50 value of 41.5 +/- 5.3 mu M, more effective compared to that of quercetin (EC50 = 81.8 +/- 8.7 mu M). The 6-OH-5,7-dimethoxy analogue (+/-)-3d showed significant inhibition of xanthine oxidase with an IC50 value of 16.0 +/- 0.8 mu M, which is superior to that of allopurinol (IC50 = 23.5 +/- 2.0 mu M). In addition to the hypothesized action mechanism of the bio-active compounds, 3D modeling was used to analyze the relationship between the minimized-energy structures and antioxidant activities. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3414 / 3425

页数：12

共 42 条

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